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Temporally and spatially regulated somatic mutagenesis in mice

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Item Type:Article
Title:Temporally and spatially regulated somatic mutagenesis in mice
Creators Name:Schwenk, F., Kühn, R., Angrand, P.O., Rajewsky, K. and Stewart, A.F.
Abstract:In mice transgenesis through oocyte injection or DNA recombination in embryonal stem (ES) cells allows mutations to be introduced into the germline. However, the earliest phenotype of the introduced mutation can eclipse later effects. We show in mice that site-specific genomic recombination can be induced in a selected cell type, B lymphocytes, at a chosen time. This precision of somatic mutagenesis was accomplished by limiting expression of a Cre recombinase-estrogen receptor fusion protein to B lymphocytes by use of tissue-specific elements in the promoter of the transgene employed. The expressed fusion protein remained inactive until derepressed by systemic administration of an exogenous ligand for the estrogen receptor, 4-OH-tamoxifen. Upon derepression the Cre recombinase enzyme deleted specific DNA segments, flanked by loxP sites, in B lymphocytes only. The efficiency of recombination in cells expressing the fusion protein could be varied from low levels to >80%, depending on the dose of ligand administered. Our work presents a paradigm applicable to other uses of site-specific recombination in somatic mutagenesis where both temporal and spatial regulation are desired.
Keywords:B-Lymphocytes, Cell Line, Estrogen Receptors, Gene Deletion, Gene Expression, Genetic Recombination, Integrases, Ligands, Mutagenesis, Recombinant Fusion Proteins, Tamoxifen, Viral Proteins, Animals, Mice
Source:Nucleic Acids Research
Publisher:Oxford University Press
Page Range:1427-1432
Date:15 March 1998
Official Publication:https://doi.org/10.1093/nar/26.6.1427
PubMed:View item in PubMed

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